Method and apparatus for acne treatment

ABSTRACT

Disclosed is a system and method for treatment of skin disorders. More particularly, the disclosed invention is directed toward the reduction of acne and acne related bacteria using low-intensity light therapy. In an illustrative embodiment, skin containing acne bacteria is treated with a series of pulses of light from a light emitting diode. The LED has a dominant emissive wavelength of about 660 nm and an energy output of about 4 mW. The acne bacteria-containing tissue is exposed to pulses from the light source about 100 times for about 250 milliseconds per pulse, with an interpulse interval of about 100 milliseconds.

This application is a continuation-in-part of copending U.S. applicationSer. No. 11/119,378, filed May 2, 2005, which is a divisional of U.S.Pat. No. 6,887,260 filed Aug. 22, 2001, which is a continuation-in-partof U.S. Pat. No. 6,283,956, filed Nov. 30, 1998.

FIELD OF THE INVENTION

The present invention generally relates to a system and method for thetreatment of sebaceous gland disorders and related skin disorders,particularly acne, acne bacteria (e.g., proprionobacteria acnes),disorders such as narrowing of the oil gland duct, increased orexcessive oil production, pore size, acne rosacea, and pore size. Inparticular, the invention relates to the treatment of acne usingphotomodulatory means with or without the use of cosmeceuticalcompositions, naturally occurring chromophores, or other light-activatedchromophores that may be applied topically to the oil gland andsurrounding tissue in combination with exposing the composition toelectromagnetic radiation.

BACKGROUND OF THE INVENTION

There are several known techniques for attempting to reduce or eliminatethe skin disorders associated with sebaceous oil glands. The primarydisorder is acne with an associated disorder of acne scarring, oilproduction, and pore size. A few of these known techniques arescientifically proven and widely accepted as effective. However, theirdegree of efficacy varies greatly. There are several processes which maybe used for treatment of sebaceous oil glands, acne bacteria (e.g.,proprionobacteria acnes), disorders such as narrowing of the oil glandduct, increased or excessive oil production, pore size, acne rosacea,and pore size. In one process the target may be duct of the gland or theoil gland itself and the treatment focuses on the treatment of sebaceousfollicles to eliminate the associated disorders. In U.S. Pat. No.6,183,773, to Anderson, which is hereby incorporated by reference, anattempt is made to treat sebaceous gland disorders using lasers whichirradiate energy activatable material, primarily laser sensitive dyes,that have been applied to the skin.

Anderson teaches a method for treating skin disorders associated withsebaceous follicles by topically applying an energy activatable materialto a section of skin afflicted with a sebaceous gland disorder, whereinthe material is activated by energy which penetrates outer layers ofepidermis. A sufficient amount of the material infiltrates the afflictedsection of skin and is exposed to sufficient energy to cause thematerial to become photochemically or photothermally activated, therebytreating the sebaceous gland disorder. In one embodiment, the sebaceousgland disorder is acne. Suitable energy sources for use in accordancewith Anderson's invention include flash lamp based sources and lasers,such as Nd: YAG, Alexandrite, flash lamp-pumped dyes and diodes. Theenergy source can be a continuous wave energy source or pulsed. In thepreferred embodiment, the energy activatable material is a lasersensitive chromophore, e.g., a chromophore which is capable of beingphotoactived by a laser, e.g., a dye. Anderson describes a particularlypreferred embodiment, wherein the chromophore is methylene blue.

Anderson's method, however, fails to take advantage of the recentdevelopments in light emitting diode technology that permits the use ofLEDs for dermatological use in place of much more expensive lasers.Further, due to the high-intensity nature of lasers, severe skin damageor other injury can occur when the light source is improperly operated.Further, the laser dyes and other topical compositions described byAnderson are expensive and require FDA approval for their intended use,making the invention expensive and time consuming to implement. Further,because of Anderson's focus on the oil gland itself, rather than theelimination of the acne bacteria, suitable results may not be achievedin all cases.

In WO 00/02491, to Harth et al., a method and apparatus are disclosedfor eliminating acne bacteria through photothermal means by exposing thebacteria to a narrow band light source in the range of 405 nm to 440 nm.Harth et al., as well, failed to appreciate the opportunity for currentLED technology to be applied to dermatologic treatment and, likeAnderson, do not disclose means for treating sebaceous oil glanddisorders without the high cost and time commitment necessary to receiveFDA approval require for high-intensity light therapies with topicalcompositions such as methylene blue.

In each of the known attempts to treat sebaceous gland disorders,extensive investment in expensive light sources and topical drugcomposition testing is required. Moreover, none of these attemptsaddresses the secondary disorder associated with acne—acne scarring.

Consequently, it would be desirable to have a treatment for sebaceousgland disorders and, in particular, acne that addresses and treats acnescarring without the need for expensive, potentially dangeroushigh-intensity light sources. Further, it would be beneficial for such atreatment regiment to include the use of naturally occuring compositionsthat fall into the category of cosmetics and cosmeceuticals that aregenerally recognized as safe and that do not require FDA approval,thereby eliminating the time and resource expenditures associated withthe commercial implementation of such a treatment regime.

SUMMARY OF THE INVENTION

The present system relates to a system and method for the treatment ofsebaceous gland disorders, generally, and is pertinent to the treatmentof acne bacteria (e.g., proprionobacteria acnes), disorders such asnarrowing of the oil gland duct, increased or excessive oil production,pore size, acne rosacea, and pore size. In an illustrative embodiment,the invention relates to the reduction or elimination of acne bacteria.

The method illustratively may comprise exposure of acne bacteria to one,or more, sources of narrowband, multichromatic electromagneticradiation. Each source may have one o more dominant emissive wavelengthsbetween about 300 nm and about 1400 nm. The source or sources ofelectromagnetic radiation may be used to treat sebaceous oil glands,sebaceous ducts, sebocytes, supporting tissue thereof, dysfunctions ornarrowing of oil gland ducts, and acne rosacea and combinations thereof.

In one illustrative embodiment of the invention, the source ofnarrowband, multichromatic electromagnetic radiation is a light emittingdiode that emits light at a dominant emissive wavelength of from about390 nm to about 1060 nm. Particular wavelengths which may be selected asthe dominant emissive wavelength may include the follow, without anypreference to be indicated by order: 400 nm, 420 nm, 430 nm, 445 nm, 590nm, 635 nm, 655 nm, 660 nm, 670 nm, 780 nm, 785 nm, 810 nm, 830 nm, 840nm, 860 nm, 870 nm, 904 nm, 915 nm, 980 nm, 1015 nm, 1060 nm, 1200 nm,and 1400 nm.

In addition, an illustrative embodiment of the invention may include theuse of a photomodulation enhancing agent applied to the tissuecontaining or surrounding the acne bacteria. For use the with thepresent system, photomodulation enhancing agents may include Vitamin C,Vitamin E, Vitamin A, Vitamin K, Vitamin F, Retin A (Tretinoin),Adapalene, Retinol, Hydroquinone, Kojic acid, a growth factor,echinacea, an antibiotic, an antifungal, an antiviral, a bleachingagent, an alpha hydroxy acid, a beta hydroxy acid, salicylic acid,antioxidant triad compound, a seaweed derivative, a salt waterderivative, an antioxidant, a phytoanthocyanin,epigallocatechin-3-ganate, a phytonutrient, a botanical product, aherbaceous product, a hormone, an enzyme, a mineral, a geneticallyengineered substance, a cofactor, a catalyst, an antiaging substance,insulin, trace elements (including ionic calcium, magnesium, etc),minerals, Rogaine, a hair growth stimulating substance, a hair growthinhibiting substance, a dye, a natural or synthetic melanin, ametalloproteinase inhibitor, proline, hydroxyproline, an anestheticsubstance, chlorophyll, copper chlorophyllin, chloroplasts, carotenoids,bacteriochlorophyll, phycobilins, carotene, xanthophyll, anthocyanin,and derivatives, subcomponents, and analogs of the above, both naturaland synthetic, and mixtures thereof.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is an illustration of the chemical structure of methylene blue.

FIG. 2 shows the chemical structure of indocyanin green.

FIG. 3 a is a representation of the general chemical structure of achlorophyll molecule.

FIG. 3 b shows the structure of chlorophyll b.

FIG. 4 a shows the general chemical structure of a porphyrin molecule.

FIG. 4 b shows the structure of porphyrin IX.

FIG. 5 a illustrates the physical structure of the ligand bond portionof a chlorophyll a molecule.

FIG. 5 b illustrates the physical structure of the ligand bond portionof a protoporphyrin IX molecule.

FIG. 6 illustrates a sweat gland and the epithelial layers of humanskin.

FIG. 7 is a graph showing the absorption spectrum of 0.03% Na Cuchlorophyllin in water.

FIG. 8 illustrates the relative absorption spectra of various naturallyoccurring chromophores.

FIG. 9 shows the absorption spectrum for human fibroblast overlayed withthe wavelengths of various, commercially produced LEDs.

FIG. 10 shows the absorption spectrum for human fibroblast overlayedwith the wavelengths of various, commercially produced LEDs, and alsothe absorption spectrum of chlorophyll a.

FIG. 11 shows the absorption spectrum for human fibroblast overlayedwith the wavelengths of various, commercially produced LEDs, and alsothe absorption spectrum of chlorophyll b.

FIG. 12 shows the absorption spectrum for human fibroblast overlayedwith the wavelengths of various, commercially produced LEDs, and alsothe absorption spectrum of indocyanin green.

FIG. 13 shows the absorption spectrum for human fibroblast overlayedwith the wavelengths of various, commercially produced LEDs, and alsothe absorption spectrum of protoporphryin IX.

FIG. 14 depicts a front view, in perspective, of a three-panel array ofLEDs for treatment in accordance with an embodiment of the presentinvention.

FIG. 15 is a perspective view of hand-held LED devices for treatment inaccordance with the present invention.

A detailed description of a preferred embodiment of the presentinvention will be made with reference to the accompanying drawings.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

The following detailed description is of the best presently contemplatedmode of carrying out the invention. This description is not to be takenin a limiting sense, but is made merely for the purpose of illustratingthe general principles of the invention. The scope of the invention isdefined by the appended claims.

In a preferred embodiment, the present invention is directed to aprocess for dermatologic treatment. Such a treatment may include thephotomodulation of sebaceous oil glands and the surrounding tissue orproducing reduction of activity or destruction in acne bacteria presenton the skin or sebaceous oil glands and supporting tissue. In anillustrative embodiment, the disclosed system and method may be used totreat acne bacteria (e.g., proprionobacteria acnes), disorders such asnarrowing of the oil gland duct, increased or excessive oil production,pore size, acne rosacea, and pore size. In an illustrative embodiment,the invention relates to the reduction or elimination of acne bacteria.

The present system and method is also contemplated for use with othertreatments to reduce or eliminate bacteria or for the disinfection ofwounds and ulcers. Representative of, but not exhaustive of, bacteriatreated according these methods are H. pylori, Chlamydia, and thevarious bacteria that grow in the mouth related to periodontal and gumdisease. Moreover, certain uses of the present invention may beeffective for viral and other related treatments. Illustrative of thesetreatments are herpes infections, blood viruses (extracorporealphoresis), nail fungi, parasites, prions and various infectious agents.

In a preferred embodiment the process produces little or no permanentinjury or damage to nearby skin tissue. Substantially only the acnebacteria present on the skin, the sebaceous oil gland and areasimmediately surrounding tissue are affected. The procedures describedherein are also advantageous for reducing the inflamed appearance ofacne pimples (e.g., acne rosacea), using combinations of light at 590 nmand 870 nm, for example. As well as for preventing or reversing scarringcaused by acne.

In order to reduce the amount of acne bacteria, a light emitting diode,or other source of narrowband, multichromatic electromagnetic radiationis supplied. A device having one, or more, LED's may be fabricated in amanner that permits even exposure of tissue infected with or otherwisecontaining acne bacteria. Typically, treatment for acne bacteria isdesirable for facial application; and, thus, a multi-paneled devicehaving an array of LED's can be used. One embodiment of such a device isillustrated in FIG. 14. In instances were self-treatment is desirable,related to the lack of negative side-effects of low-intensity lighttherapy, a home treatment device as illustrated in FIG. 15 may be used.

As described in more detail below, variables that determine the efficacyof the acne treatment include the power output of the LED array andenergy fluence delivered to the bacteria; the “pulse code” of the arrayor the use of a continuous wave, and the wavelength or wavelengthsemployed by the array (in instances where multiple wavelengths are usedsimultaneously).

For use in killing acne bacteria, it has been found that light having awavelength of from about 475 nm to about 660 nm is desirable, althoughwavelengths of from about 300 nm to about 1400 nm may be used inconnection with procedures for reducing or eliminating acne bacteria.The power output of the light source may be from about 0.01 mW to about20 W, although as higher power is used, greater risk of thermal injuryto the target tissue ensues. In an illustrative embodiment of theinvention, power outputs of from about 1 mW to about 20 mW are used andthermal injury to the tissue is avoided by carefully limiting the timefor which the skin is exposed.

The treatment may be delivered in various modes. A first mode, whereintreatment is applied by exposing the acne bacteria, or tissue or glandharboring the bacteria, to a continuous wave of light, may be used.Treatment times of from about 1 minute to about 1 hour may be used,although a treatment time of from about 5 minutes to about 30 minuteshas been shown to increase the reduction of acne bacteria whileminimizing the risk of thermal injury to the skin.

A second mode of treatment, which may be referred to as intermittent or“pulsed” treatment, may also be used. In this mode of treatment, theacne bacteria, or gland or tissue harboring the bacteria, is exposed toa series of pulses from the light source. A pulse code may be referredto which identifies the pattern of pulses. For example, a pulse code of250-100-100 may be used; and refers to pulse lengths of 250milliseconds, 100 milliseconds between each pulse, and 100 pulserepetitions (respectively). Pulse codes from 1-1-1 to about1000-1000-1000 are contemplated.

As well, combinations of the various modes may be employed as cancombinations of light sources within an array for treating tissue foracne bacteria. For example, it may be desirable to combine multiplewavelengths, as shown in the examples below, to achieve more efficienttreatment. The multiple wavelengths may include combinations of light inthe visible spectrum, combinations of visible and infrared orultraviolet light, or combinations of non-visible light. In oneillustrative embodiment of the invention, a combination of yellow andinfrared light may be used to augment the bacteria reduction achieved by660 nm light with heat produced by light in the infrared region (>700nm).

Various single wavelengths and combinations of wavelengths, maydemonstrate effective treatment according to the present invention. Suchcombinations may, generally, include red/blue, red/yellow,red/yellow/IR, red/blue/yellow/IR, red alone, etc. as well as sequencesof pulsed or continuous waves of light having dominant emissivewavelengths corresponding to these colors. As well, each of thesecombinations may be more effective for certain skin types of particulartreatments, depending on whether they are used with or without heatapplication to the skin. Without preferences as to order, the followingwavelengths may be used alone or in combination, simultaneously orsequentially, pulsed or in a continuous wave, and with or without heat,in accordance with the present system and method: 400 nm, 420 nm, 430nm, 445 nm, 475 nm, 590 nm, 635 nm, 655 nm, 660 nm, 670 nm, 780 nm, 785nm, 810 nm, 830 nm, 840 nm, 860 nm, 890 nm, 904 nm, 915 nm, 980 nm, 1015nm, 1060 nm, 1260 nm, and 1400 nm.

Further, topical compositions and treatments that permit greaterpenetration of the light into the skin, allowing it to reach thesebaceous oil glands may be used. For example, according to anillustrative process according to the present invention, an agent may beselected which is capable of penetrating the oil gland and surroundingtissue. The agent may be characterized as an active agent in that itperforms a function in addition to simply occupying or contaminating thespace in the ducts surrounding the gland. Alternatively, the agent mayperform the passive function filling the void space in the ductssurrounding the glands, depending on the nature of the treatmentdesired. The agent may have sufficient optical absorption of awavelength (or a combination of wavelengths) of a coherent ornon-coherent light source which can penetrate the skin adequately to beabsorbed by the target agent or the new agent-tissue complex.

The area of skin overlying where the oil gland is located may becleansed. After the skin is cleansed, the skin may be treated to improvepermeability. This may be accomplished, for example, by treating theskin with steam or a hot moist towel to hydrate the skin and hair orremoving a portion of the stratum corneum through various means known inthe art, exemplary of which is microdermabrasion.

The agent may be applied in sufficient quantity and in suitable form tobe incorporated into the target tissue in adequate or optimal amounts toallow the production of the desired tissue effect.

Excess agent may be removed, neutralized, inactivated, decolorized,diluted or otherwise altered so that residual contamination of the skinby such excess agent is either (a) absent and does not interact with thelight or energy source, or (b) present in such small quantity that itprovides no clinical effect.

Delivery of the desired agent into the target tissues may be enhanced,facilitated or made possible by the use of enzymes capable of alteringthe structure, permeability, or other physical characteristics of thestratum corneum or by the use of ultrasound or phonophoresis either forpenetration into the gland or surrounding target tissues or, oncepenetrated, to cause the release of the agent from the encapsulateddelivery device such as liposomes, polymers, microspheres, etc. so as tocause penetration or attachment of this active agent. Ultrasound may beused therapeutically to interact directly with the agent or theagent-tissue complex to produce the desired damaged target tissues (tobe used alone or in combination with laser or non-laser light sources).Microdermabrasion may also be used to permit greater penetration of theskin, wherein the upper epithelial layers are removed. These layerscreate a natural barrier to the permeability of the skin and. by theirremoval, penetration of the skin by topical agents is facilitated. Thismethod may be further enhanced by using ultrasound, alone or incombination with alteration of the stratum corneum, to further improvethe performance of topical compositions. A more detailed description ofseveral aspects of the use of ultrasound may be found, for example, inthe applicant's U.S. Pat. Nos. 6,030,374 and 7,004,933, each entitled“Ultrasound Enhancement of Percutaneous Drug Absorption” which arehereby incorporated by reference in their entirety.

Although preferred embodiments of the present invention may use LEDs,ultrasound and/or laser or light energy, the present invention is notlimited to the use of these energy sources. Other sources of energy,including (without limitation) microwave energy and radio frequencyenergy may also be used. Exemplary of known light sources arefluorescent lights, flashlamps, filamentous lights, etc. One skilled inthe art will recognize that any light source capable of emittingelectromagnetic radiation at a medically useful wavelength, as describedherein, directly, or by means of optical filtration, is within the scopeof suitable light sources according to the present invention. Forpurposes of the photomodulatory and photothermal treatment methodsdescribed, any source capable of emitting light having a wavelength fromabout 300 nm to about 1400 nm, or producing electromagnetic radiationwhich is filtered or otherwise altered to exposure the skin, a topicalcomposition, or other component of the present treatment regime to awavelength of light in the aforementioned range is medically useful.

The targeted skin may be exposed to one or more wavelengths of LED,laser or non-laser light such as filtered filamentous sources orfluorescent sources or single or multiple frequencies of ultrasound. Theskin, bacteria, or tissue that is targeted may be exposed to light thatis pulsed or in a continuous wave, sequenced or simultaneous, andinclude one or more wavelengths. Heat may, optionally, be employed witheach treatment regimen. As well, unless otherwise specified hereinafter,the energy fluences recited herein refer to the amount of energy(watts×time) perceived by the targeted tissue, cell, or other biologicalstructure being treated. Typical energy fluences may range from about0.01 J/cm² to about 20 J/cm². Non-thermal treatment, however, may employan energy fluence of about 0.01 J/cm² to about 7 J/cm², in the absenceof the use of skin cooling means. Skin cooling means may, as well, beemployed with the various illustrative embodiments of the inventiondescribed here.

A variety of parameters may be used (including pulse duration, energy,single or multiple pulses, the interval between pulses, the total numberof pulses, etc.) to deliver sufficient cumulative energy to interactwith the agent or tissue complex. This results in the inhibition ordestruction of the sebaceous oil gland or the supporting skin tissuethrough photomodulatory means, photothermal means, or combinationsthereof. Ultrasound may also be used to preheat the target structures orthe entire skin. Further for treatment over a broad area of human skin,the light source may be diffused through a device such as a holographicdiffuser; or, alternatively, the light source may be comprised of anarray of individual emitters such as the three-panel array of LEDsillustrated in FIG. 14. For localized treatment, smaller arrays orindividual LEDs, such as in the hand held devices depicted in FIG. 15may be used. Since LED sources are considered “insignificant riskdevices”, no medical supervision is required and these devices may beused by the patient for at-home treatment or as part of an ongoingskin-care system after receiving treatment by a physician.

The following table illustrates the results of tests conducted inaccordance with the present invention, at varying wavelengths and powerlevel. For each, it is shown whether a pulsed or continuous wave (CW) isemployed. The efficacy is determined by the reduction in acne bacteriacount observed in each sample, after being exposed to the regiment oflight treatment shown in the leftmost column. TABLE 1 Acne BacteriaCount Reduction Total Acne Bacteria AVG AVG # of Wells Counts CountReduction 475 nm (250/100/100) Pulsed@4 mW 13 828 63.69 34.75% 475 nm(250/100/100) Pulsed@14 mW 11 896 81.45 16.55% 475 nm 15 min CW@4 mW 12662 55.17 43.48% 475 nm 15 min CW@14 mW 9 634 70.44 27.83% 590 nm/870 nm(250/100/100) 16 1220 76.25 21.88% Pulsed@4 mW 590 nm/870 nm(250/100/100) 16 1563 97.69 −0.08% Pulsed@6 mW 590 nm/870 nm 15 min CW@4mW 12 977 81.42 16.59% 590 nm/870 nm 15 min CW@6 mW 12 1016 84.67 13.26%660 nm (250/100/100) Pulsed@4 mW 12 380 31.67 67.56% 660 nm(250/100/100) Pulsed@14 mW 12 738 61.50 36.99% 660 nm 15 min CW@4 mW 8200 25.00 74.39% 660 nm 15 min CW@14 mW 8 514 64.25 34.17% 635 nm(250/100/100) Pulsed@4 mW 12 725 60.42 38.10% 635 nm (250/100/100)Pulsed@16 mW 8 442 55.25 43.40% 635 nm 15 min CW@4 mW 8 743 92.88 4.85%635 nm 15 min CW@16 mW 8 655 81.88 16.12% Control Plates 61 5954 97.610.00%

In connection with each of the treatments already disclosed, a topicalagent may also be applied to the target bacteria, tissue, or skin. Aselected composition may be applied to, or into, the target tissue by avariety of mechanisms. These mechanisms include, but are not limitedto: 1) physical incorporation into the gland or target tissue cellswhile leaving the chemical structure essentially unaffected, or 2)undergoing a chemical reaction resulting in a new agent-tissue complexwhich then becomes a target for energy absorption.

The process may be a single or multi-step process and may involve theuse of cofactors, catalysts, enzymes, or multiple agents which interactto ultimately become or create an active agent or agent-tissue complex.

Agents may include, without limitation, the following compositions andderivatives and analogs thereof: hair dyes, vegetable dyes, foodcoloring, fabric dyes, tissue stains, shoe or leather dyes, other plantproducts (such as flavonols, chlorophyll, copper chlorophyllin, bacteriachlorophylls, carotenoids, enzymes, monoclonal antibodies, anyimmunological agent, genetically engineered agent, benign infectiousagents, whether naturally occurring or genetically engineered (e.g.various bacteria that normally reside on the skin such as acne bacteria,etc.), antibiotics, agents which attach to sebocytes in the sebaceousgland or duct cells directly, whether by topical or systemic agents thatlocalize in these target tissues, including antibodies orantibody-chromophore compounds of these structures. The preceding listis illustrative and not exhaustive of those agents suitable for use inaccordance with the present invention. In general, the topical agentchosen will have certain absorption characteristics that augment thepenetration of the radiation to the tissue targeted for treatment, i.e.,sebaceous oil gland, acne-scarred tissue, etc.

Most preferable are topical compositions that include a quantity of anaturally occurring chromophore such as chlorophyll, chlorophyllin,polyporphyin, bacteriochlorophyll, protopolyporphyin, etc. Thesecompositions are characterized by a metal-ligand bond as is illustratedin FIGS. 3 b and 4 b, specifically, and in FIGS. 3 and 4 more generally.Further, FIGS. 5 a and 5 b show the metal-ligand bond physical structurethat is common to the naturally occurring native chromophores of thepresent invention, as well as the cyclic tetrapyrrole ring thatchlorophyll shares with suitable cytochromes. In contrast, syntheticchromphores do not include a metal-ligand bond, nor do they exhibit thesame general physical structure as naturally occurring chromophores, asis illustrated by the structure of methylene blue, FIG. 1, andindocyanin green, FIG. 2.

Agents may be delivered in pure form, in solution, in suspension, inemulsions, in liposomes, in synthetic or natural microspheres,microsponges or other known microencapsulation vehicles, alone or incombination. This list of the forms of the agents is illustrative andnot exhaustive. Those skilled in the art will recognize that there are awide variety of forms for the delivery of topical compositions suitablefor use in accordance with this invention.

The process may include an application of an active agent and treatmentwith an energy source as a single treatment. Alternatively, treatmentwith an energy source may be delayed for hours or days after applicationof an active agent. Application of an active agent may be performed orapplied at another location, such as patient's home, prior to the energytreatment.

After an energy treatment has occurred it may be desirable in somesituations to remove, neutralize, decolorize or otherwise inactivate anyresidual active agent. In other situations, continued application toreplenish depleted chromophore may be desirable.

One preferred embodiment uses the transdermal application of chlorophyllto the sebaceous oil gland and surrounding tissue. The chlorophyll isthen exposed to a source of electromagnetic radiation such as from alaser, an LED, a flash-lamp, or other source filtered to provide adominant wavelength of from about 400 nm to about 450 nm. Otherpreferred wavelengths include from about 360 nm to about 440 nm and,with greater preference, from about 380 nm to about 420 nm. Pulsedurations may be selected with sufficient power density to allow thetarget tissue to be appropriately inhibited to reduce acne bacteriacontent and to reduce or destroy gland activity through photomodulationand photothermal means. While blue light is used for illustrativepurposes, it has been found that red light is also effective inaccordance with the present invention. Generally, one skilled in the artwill recognize to choose a light wavelength for treatment in the rangeof about 300 nm to about 1400 nm based on the absorption spectrum of thechromophore or other light-activated topical composition used. FIG. 7shows the absorption spectrum for 0.03% Na Cu Chlorophyllin in deionizedwater. The primary absorption peak is shown to be at around 400 nm. Thiswould indicate that for this chromophore, the most suitable wavelengthfor photomodulator and/or photothermal treatment would be at around 400nm. Another absorption peak occurs at around 620 nm, thus in an instancewhere a light source with a dominant wavelength of around 400 nm was notavailable, a light source with a dominant wavelength of around 620 nmcould be used. This figure further illustrates the absorption spectra ofa carotenoid with a broad absorption band from 400 nm to 520 nm. Thisallows use of more wavelengths including those of green light (500 nm to520 nm). A comparison of the absorption spectra of various naturallyoccurring chromophores is shown in FIG. 8.

One acne treatment process uses a solution of graphite in a carriersolution and a Q-switched 1064 nm ND:YAG laser. The solution may beapplied to the skin which is then treated with the laser using knownparameters. It may be preferable to use a high repetition rate and movethe laser handpiece slowly enough that pulses are “stacked’ in one spotfor several pulses before the handpiece is moved to an adjacent spot. Ithas been found that there is a stair-step like effect of incrementaltemperature rise in the sebaceous glands with the second and thirdpulses versus a single pulse. A faster repetition rate also tends tohelp build the heat up faster, and to higher levels. This tends toproduce the maximum heat (which is desirable, as long as the heat staysconfined to the sebaceous glands and the immediately adjacent supportingtissues). Since this effect occurs substantially simultaneously withother destructive effects of the process, the damage to sebaceous glandstends to be enhanced. Unlike carbon exploded particles on light impact,the dyes and similar agents may actually remain absorbing for a brieftime until they reach a critical temperature at which time they aredestroyed or become non absorbers, thus acting as a sort of heat sinkfor a brief time, allowing more heat to accumulate than with carbonsolutions and short pulsed Q-Switched lasers. Safety remains at aboutthe same level, since dye related damage tends to be confined to targettissues. There is no appreciable change in patient treatment time.

Another preferred embodiment uses a longer pulsed laser in the750nm-1000 nm range and appropriate parameters to achieve the desiredtissue damage goal.

Another embodiment uses a tissue dye which attaches to, or isincorporated into, a target cell and surrounding tissues. The targettissue may be illuminated with a multi-wavelength non-laser light sourceusing appropriate parameters to achieve the desired tissue damage goal.

Another embodiment uses a light source which is well-absorbed by themelanin naturally present in skin and undyed darker hairs. Natural orsynthetic melanin or derivatives thereof will be well-absorbed by thesame wavelength of light (or alternatively two or more wavelengths, onefor melanin and one or more for the dye). This melanin agent isdelivered into the sebaceous gland, duct, or supporting tissue,resulting in an enhanced or greater injury to the target tissue (orpermitting lower treatment energy parameters, resulting in safertreatment than if the sebaceous gland, duct, or supporting tissue weretreated without the melanin dye). This tends to benefit people havingdarker skin or tanned skin, by allowing lower treatment energy. Forexample, a diode laser or LED or non-laser light source could produce acontinuous or pseudo-continuous beam of light energy using pulsedurations as long as seconds at a wavelength which is absorbed by thelight-activated chromophore, native porphyrin containing acne bacteriaporphyrin compound, or native sebaceous gland, duct, or supportingtissue pigment and also by the melanin or dye used. A pulse duration onthe order of between about one and thirty seconds appears to bepreferable. This also tends to be a much longer time than is used inmost systems in use today.

Another embodiment uses an agent which facilitates cavitation shockwaves or a thermal effect or both. This preferentially damages (orstimulates) the target tissues while minimizing damage (or other adverseeffects) on surrounding non-target tissues. This may be used with veryshort pulsed lasers or light sources or with ultrasound alone.

In one embodiment a process in accordance with the present invention maybe used to provide short or long-term control, improvement, reduction orelimination of acne or other related skin diseases. An active agent maybe physically or chemically or immunologically incorporated into cellsof the sebaceous (oil) glands, ducts, or supporting tissue, or into thenaturally occurring acne bacteria, porphyrin compounds, naturallyoccurring light activated chromophores, yeast or similar organisms whichfeed on the oil in the oil glands (or sweat glands) or exists in the oilor oil glands as otherwise relatively benign inhabitants. Some acnebacteria may not inhabit all sebaceous structures and other strains maynot produce native porphyrins to target with light. Other acne bacteriamay be located deeper than 400 nm to 420 nm light can adequatelypenetrate, thus treatment with light alone may be only partiallyeffective in clinical treatment. Improvement in skin disorders may be adirect or indirect result of the application of the agents in thisprocess, as may reduced oiliness of the skin, reduced size or diminishedappearance of pores, etc. The present invention is also useful fortreating enlarged pores, oily skin, and other disorders where there isno active acne-related disorder.

Other similar disorders such as folliculitis which involve thepilosebaceous (hair/oil gland) unit may also be treated using thepresent invention. The present invention may also be used to reduceperspiration, sweating, or hyperhidrosis from eccrine (sweat) glands orapocrine glands. A preferred embodiment of the present invention may beused to treat other skin disorders such as, for example, viral warts,psoriasis, precancerous solar keratosis or skin lesions,hyperhidrosis/excessive sweating, aging, wrinkled or sundamaged skin,and skin ulcers (diabetic, pressure, venous stasis).

Scarring is commonly seen as a consequence of disorders, diseases, ordysfunctions of the sebaceous apparatus. Scarring may consist of one ormore of the following: raised hypertrophic scars or fibrosis, depressedatrophic scars, hyperpigmentation, hyperpigmentary redness ortelangectasia. Photomodulatory, photochemical, or photothermaltreatments alone, or in combination with exogenous or endogenouschromophores, or combinations thereof, can be used simultaneously,sequentially, etc., as described herein for the treatment of sebaceousgland disorders, diseases, or dysfunctions to prevent or reduce scarringbefore it occurs, or to reduce previously existing scarring.

Further, as herein described, the term photomodulation refers to thetreatment of living tissue with light along, heat emitted by a lightsource, or light-activated chemical compositions, or any combinationthereof. Falling within the scope of photomodulatory treatments arephotothermal treatment, photoactivation, photoinhibition, andphotochemical treatment of living tissue and, in particular, sebaceousstructures within human skin. Further, electromagnetic emitters of thepresent invention can fall into three categories: those which emit lightin the visible spectrum and are useful for photoactivation andphotoinhibition photomodulatory process; those that emit light in theultraviolet spectrum and are also useful for photoactivation andphotoinhibition photomodulatory process; and those that emit light inthe infrared region and permit photomodulation treatment to be carriedout through photothermal means, i.e., heat activation of the exogenouschromorphore, living cells or tissue, or both.

A preferred embodiment of the present invention may use variousmicroencapsulation processes to deliver active agents. If the diameterof the micro encapsulations is about five microns, then there may berelatively site specific preferential delivery into the sebaceous oilglands or skin surface stratum corneum cells. If the diameter of themicroencapsulations is in the range of about one micron, then the activeagents may be delivered with a more random distribution between the hairducts and the oil glands. If the diameter of the microencapsulations islarger, on the order of about 20 microns or greater, then delivery willtend to be restricted primarily to the skin surface. The microencapsulations may be synthetic or natural. If ultrasound is used toenhance penetration, then the diameters and ultrasound treatmentparameters may need to be adjusted according to the applicableprinciples which allow the estimation of the optimal ultrasoundparameters for driving small particles into the skin, skin appendages orskin orifices.

Microencapsulation may be used to improve delivery of known agents suchas chlorophyll, carotenoids, methylene blue, indocyanine green andparticles of carbon or graphite. A known technique for using a laser toproduce a wavelength that may be absorbed by indocyanine green for ahair removal treatment process is described, for example, in U.S. Pat.No. 5,669,916, which is incorporated by reference. It has been foundthat by using smaller particles and putting the smaller particles intomore uniform diameter microencapsulations, more site specific or uniformtargeting may be achieved. A preferred formulation may includeindocyanine green or other dyes or agents to form a lipid complex whichis fat-loving (lipophilic). The delivery and clinical effects of agentsand dyes such as indocyanine green dye may be refined and enhanced byselecting a carrier or encapsulation having a diameter that increasesthe probability of preferential delivery to a desired space, and/or thatenables interaction with ultrasound to thereby increase the probabilityof preferential delivery, and/or that selectively attaches to thesebaceous gland, duct, supporting tissues, oil itself or bacteria,yeasts, or other organisms residing within these tissues.

Indocyanine green dye is presently in medical use, appears to berelatively benign, may be activated by red visible lasers, or othersource of monochromatic or multichromatic light, (in the 800 nm range)may penetrate deeply enough to reach the oil glands, is used for legvein and hair removal, and is relatively safe, cheap, and reliable. Aknown technique for using a laser to produce a wavelength that may beabsorbed by indocyanine green for use in a leg vein treatment process isdescribed, for example, in U.S. Pat. No. 5,658,323, which isincorporated by reference. Methylene blue has also been used accordingto the present invention with good success.

The microsponges containing the active agent may selectively attach, orat least have a chemical affinity for, some part of the oil gland. TheICN dye may be conjugated with lipids, which would then have an affinityfor the oil glands. Alternatively, the attachment may occur after theactive agent is released from the microsponge, either passively or byattractive or chemical forces. In the case of some microencapsulationcarrier vehicles, release may occur after disruption of the vehicleintegrity itself, possibly by ultrasound or laser or light or otherenergy source or perhaps a chemical reaction.

In a preferred embodiment the ICN dye may be mixed with lipids, or putinto microsponges (a.k.a. microspheres), and then applied to the skinsurface, allowed to sit for a time. Excess dye may be removed, and thenthe area may be treated with laser light at about 800 nm, between about0.1 and 100 millisecond pulses and around 1.0-10.0 Joules/cm².

U.S. Pat. No. 5,817,089 specifies “particles having a major diameter ofabout 1 micron”. It has been discovered, however, that these diametersmay not be optimal. A 1993 Pharmaceutical Research journal article byRolland et al describes an acne treatment wherein a topical acne drug isdelivered with less irritation by putting the drug into syntheticpolymer microsphere sponges. This article reported that an optimaldiameter for site-specific delivery into sebaceous oil glands in theskin was about 5 microns, and that 1 micron particles randomly deliveredto the hair follicle and stratum corneum.

Most agents may not inherently be the optimal size. However, virtuallyany agent may be preferentially delivered to the sebaceous glands byeither synthetic microspheres, or liposomes, or albumen microspheres, orother similar “delivery devices”.

In a preferred embodiment for treatment of acne, graphite particleshaving an average diameter of about one micron may be placed in deliverydevices, such as microsponges, having an average diameter of about fivemicrons. The microsponges may then be suspended in a lotion. Ultrasoundmay be used to drive the particles into the skin. The optimal ultrasoundparameters may be based on the outside particle diameter (especially ifparticles are uniform). Selective delivery of the particles to hair andperhaps to sweat glands may be improved.

Use of such applications could enable selective delivery of anti-acneagents, or hair dye for laser hair removal, or agents which stimulatehair growth, or other hair treatments, where the encapsulation diameterwas used, with or without ultrasound, to preferentially deliver, andultrasound at different parameters or laser was used to release (notnecessarily to activate or interact).

These techniques may be applied to many other agents in addition to ICNdye and graphite lotions. The term “encapsulated delivery device” isused herein as a generic term which encompasses all such possible items.

Pressure may be used to impel particles (i.e., graphite, carbon, orother active agent or skin contaminant particulates) into the skin,either in the spaces between the stratum corneum, into the hair ductsand hair follicles, the sebaceous oil glands, or other structures. Airpressure or other gases or liquids may be used to enhance delivery orincrease the quantity of delivered agent. A known technique for using anair pressure device for removing skin surface is described, for example,in U.S. Pat. No. 5,037,432, which is incorporated by reference.

Ultrasound may be used to physically deliver hair dye and to enhancepenetration into the hair shaft itself (see, for example, U.S. Pat. No.5,817,089, incorporated herein by reference and U.S. Pat. No. 7,004,933,which as already been mentioned). The use of ultrasound to physicallydrive graphite particles down for the treatment of unwanted hair or acneappears to have been suggested in the prior art. However, the applicantis aware of no prior art disclosure or suggestion of: (1) the use ofultrasound to enhance the penetration of an agent into the hair shaftitself, or into surrounding cells; (2) the use of ultrasound to drivegraphite particles into spaces between the stratum corneum to enhancethe effects of a skin peel process (which physically removes a portionof the outer layers of the skin surface); or (3) physically removing thehair by methods such as waxing or pulling and then injecting thetreatment composition, i.e., the chromophore or other topicalcomposition, into the sebaceous gland or duct. Such methods arecontemplated in one embodiment of the invention.

A known skin peel process may be improved by using ultrasound to openintercellular spaces in the outer stratum corneum layer of the skin viacavitation. Then an active agent may be driven in further with the sameor similar ultrasound. Fibroblast stimulation may be optimized with bothtopical agents that are applied afterwards (while the skin is stillrelatively permeable) and also with additional low level lightstimulation.

The processes described above may be used to deliver two differentagents, either serially or simultaneously. The two agents may then beactivated by the light source together to work synergistically, or tocombine and then have an effect, or to deliver two different agents thatmay be activated simultaneously or very closely in time. Two differentlight sources or wavelengths may be used serially or simultaneous tohave different effects such as treating active acne lesions and alsoacne scarring; treating acne rosacea lesions and also rosacea bloodvessels or telangectasia; or using photothermal means for active acneand nonthermal photomodulation for treating acne scarring or skinwrinkles.

Two entirely different laser, LED, or light beams may be deliveredsubstantially simultaneously through the same optics at differentparameters. For example, one beam may be delivered primarily to releaseor to activate, and a second beam primarily to treat. Additive effectsmay be achieved by using two beams at the same time, such as the use ofblue light with a wavelength of approximately 425 nm and red light witha wavelength of approximately 660 nm. For example, a known process forskin peel and hair reduction may be optimal at 1064 nm for safety andfor treating all skin colors, but other wavelengths may be better toachieve a low level laser stimulation of fibroblasts. Acne reduction isachieved by this process, as well, using lasers or LEDS as the low-levellight source at a wavelength chosen according to the absorption spectrumof the topical composition used. Particularly preferred for topicalcompositions are those comprising naturally occurringchlorophyll-containing compounds, carotenoid-containing compounds,derivatives thereof, and mixtures thereof, as well as derivatives,analogs, and genetically engineered forms of such agents.

A hand-held device containing the low-level light source may be used tophotomodulate or photothermally activate, or both, the living tissue oractive ingredient in the topical composition, or both, for skin peel,hair reduction, or acne reduction, and either simultaneous orsynchronized sequentially in time to deliver another wavelength that maybe optimal to in view of the absorption characteristics of the patient'sfibroblast spectrum or the spectrum of the topical composition. In theone case it may be the best wavelength to stimulate fibroblasts. Inanother case it may allow selection of a melanin or dye (or other agent)having very strong affinity for the sebaceous gland and very strongabsorption at the wavelength used for treatment.

There are a wide variety of different operating parameters that maycomprise conditions effective to produce beneficial cellular effectssuch as triggering cellular regeneration or photoactivation orphotoinhibition which, for example, could reduce the activity of, oreven destroy, oil glands in the skin, thereby indirectly reducing acnebacteria. Also, it is preferable to target a natural chromophore forphotoactivation or photoinhibition, each falling under the general termphotomodulation is possible for directly treating the naturally occuringporphyrin compounds in acne bacteria, in addition to targeting exogenouschromophores like carotenoids, chlorophyll and its derivatives includingcopper chlorophyllin and other dyes such as indocyanine green dye,methylene blue dye, and similar compositions known to those skilled inthe art. Further photothermal modulation of the oil glands andsurrounding tissue can be accomplished via the same means as describedabove, although the operating parameters may vary. The difference beingthat photothermal treatment uses heat to induce minor to moderateamounts of thermal injury to the gland or surround tissue to reduce theactivity of the target tissue or destroy it altogether.

Exogenous chromophores are substances which absorb light orelectromagnetic radiation in at least one narrow band of wavelengths andassist with the treatment method and system of the present invention byapplying them to an area of the skin to be treated. Selection of theexogenous chromophore is determined by the absoroption spectra of thechromophores and is dependent on the wavelength of the narrowbandmultichromatic emitter used for treatment. In accordance with apreferred embodiment of the invention, the chromophore will aid intreatment by enabling at least the dominant or central wavelength of thenarrowband, multichromatic radiation to penetrate at least the stratumcorneum layer of the skin and permitting the photomodulation orphotothermal injury or destruction of living tissue, sebaceous oilgland, duct, or supporting tissue in and below the stratum corneum. Insome instances, the photomodulated tissue can be below all of theepithelial layers of the skin.

Some examples of possible operating parameters may include thewavelengths of the electromagnetic radiation to which the living tissuecontaining cells to be regenerated, stimulated, inhibited, or destroyed,the duration of pulses (pulse duraction) of the electromagneticradiation, the number of pulses, the duration between pulses, alsoreferred to as repetition rate or interpulse interval. Intervals betweentreatments can be as long as hours, days, weeks, months, etc.; and thetotal number of treatments is determined by the response of theindividual patient. Further, treatment regimens using a combination ofmore than one wavelengths either simultaneous or in sequence may beused. As well, the energy intensity of the radiation as measured at theliving tissue (typically measured in Joules per centimeter squared,watts per centimeter squared, etc.), the pH of the cell, tissue or skin,the skin temperature, and time from application to treatment with alight source, if used with exogenous chromophore (which can be topical,injected, driven in with ultrasound, or systemic) is determined by thenature of the treatment and is further illustrated in the Examples.

Wavelength—Each target cell or subcellular component, or molecular bondtherein, tends to have at least one unique and characteristic “actionspectrum” at which it exhibits certain electromagnetic or lightabsorption peaks or maxima FIG. 3, for example, shows the absorptionspectrum of one line of human fibroblast cells in monolayer tissueculture. Different cell lines (of the same cell—for example fibroblastsfrom 3 different patients) exhibit some differences in their absorptionspectra and thus using narrow band multichromatic light (rather thanmonochromatic light) is also useful in producing the optimal clinicaleffect. When these cells or subcellular components are irradiated withwavelengths corresponding to the absorption peaks or maxima, energy istransferred from the light photon and absorbed by the target. Theparticular features of the delivered energy determine the cellulareffects. The complexity of these combinations of parameters has producedmuch confusion in the prior art. Basically, the wavelength shouldroughly correlate with an absorption maxima for the target cell orsubcellular component or tissue, or exogenous chromophore. In some casesit may be desirable to target more than one maxima—either simultaneouslyor sequentially on the same or different treatment dates. The presenceof multiple maxima action spectra are common for a given cell orsubcellular component or exogenous chromophore and different wavelengthmaxima irradiation may produce different results.

If the wavelength band is overly broad, then the desired photomodulationeffects may be altered from those intended. Consequently, use of broadband noncoherent intense light sources may be less desirable than thosespecified for use with the present invention, in contrast to the use ofmultiple narrowband emitters. The laser diodes are also multichromaticwith narrow wavelength bands around a dominant band, i.e., they arenarrowband multichromatic devices—devices which emit electromagnetic ina narrow band of radiation either symetrically or asymetrically around adominant wavelength. For purposes of the present invention, any devicethat emits electromagnetic radiation in a bandwidth of +/−about 1000nanometers around a dominant wavelength can be considered to be anarrowband, multichromatic emitter. LEDS, while not monochromatic, emitin such a narrow band as to be considered narrowband multichromaticemitters. The narrow band allows photons of slightly differentwavelengths to be emitted. This can potentially be beneficial forcreating certain desirable multi photon interactions. In contrast, mostcommercial lasers emit light at a single wavelength of light and areconsidered monochromatic. The use of lasers, according to the prior art,has relied upon the coherent, i.e., monochromatic, nature of theirelectromagnetic emissions.

Wavelength may also determine tissue penetration depth. It is importantfor the desired wavelength to reach the target cell, tissue or organ.Tissue penetration depth for intact skin may be different than thetissue penetration depth for ulcerated or burned skin and may also bedifferent for skin that has been abraded or enzymatically peeled or thathas had at least a portion of the stratum corneum removed by any method.It is also important to penetrate any interfering chromophore that alsoabsorbs at this same wavelength (e.g. dark ethnic skin, plastic Petriedishes for tissue or cell culture, etc.). It is important to penetrateany tissues or organs in its pathway.

For example, light having a dominant wavelength emission in the range ofabout 400 nm to about 475 nm has such a short wavelength that not allsebaceous glands or acne cysts can be effectively treated due to thelimited depth of penetration of the radiation, whereas light having awavelength of about 600 nm to about 660 nm can more easily penetrate toa greater depth, if treatment of the lower dermal layers or even deeperis desirable. Accordingly, the selection of the dominant wavelength ofthe radiation emitter is also dependent on the depth of treatmentdesired. The selection of the proper wavelength is one of thesignificant parameters for effective use of the present invention, butothers are important as well:

Energy Density—The energy density corresponds to the amount of energydelivered during irradiation and is also referred to as energy intensityand light intensity. The optimal ‘dose’ is affected by pulse durationand wavelength—thus, these are interrelated and pulse duration is veryimportant—in general high energy produces inhibition and lower energyproduces stimulation.

Pulse duration—The exposure time for the irradiation is very criticaland varies with the desired effect and the target cell, subcellularcomponent, exogenous chromophore tissue or organ.(e.g. 0.5 microsecondsto 10 min may be effective for human fibroblasts, though greater orlesser may also be used successfully).

Continuous Wave (CW) vs. pulsed—e.g. the optimal pulse duration isaffected by these parameters. In general, the energy requirements aredifferent if pulsed mode is used compared to continuous (CW) modes.Generally, the pulsed mode is preferred for certain treatment regimenand the CW mode for others.

Frequency (if pulsed)—e.g. higher frequency tends to be inhibitory whilelower frequency tends to be stimulatory, but exceptions may occur.

Duty cycle—This is the device light output repetition cycle whereby theirradiation is repeated at periodic intervals, also referred to hereinas the interpulse delay (time between pulses when the treatment sessioncomprises a series of pulses).

Suitable active agents for use in topical compositions applied to theskin in accordance with the present invention include one or more ofVitamin C, Vitamin E, Vitamin D, Vitamin A, Vitamin K, Vitamin F, RetinA (Tretinoin), Adapalene, Retinol, Hydroquinone, Kojic acid, a growthfactor, echinacea, an antibiotic, an antifungal, an antiviral, ableaching agent, an alpha hydroxy acid, a beta hydroxy acid, salicylicacid, antioxidant triad compound, a seaweed derivative, a salt waterderivative, algae, an antioxidant, a phytoanthocyanin, a phytonutrient,plankton, a botanical product, a herbaceous product, a hormone, anenzyme, a mineral, a genetically engineered substance, a cofactor, acatalyst, an antiaging substance, insulin, trace elements (includingionic calcium, magnesium, etc), minerals, Rogaine, a hair growthstimulating substance, a hair growth inhibiting substance, a dye, anatural or synthetic melanin, a metalloproteinase inhibitor, proline,hydroxyproline, an anesthetic substance, chlorophyllbacteriochlorophyll, copper chlorophyllin, chloroplasts, carotenoids,phycobilin, rhodopsin, anthocyanin, and derivatives, subcomponents,immunological complexes and antibodies directed towards any component ofthe target skin structure or apparatus, and analogs of the above itemsboth natural and synthetic, as well as combinations thereof.

While not a limiting factor, a common aspect of the most useful naturalchromophores of the present invention is found in their chemicalstructure. Naturally occuring chromophores have a metal-ligand bondingsite. FIG. 2 illustrates the chemical structure of chlorophyll a,characterized by R═CH₃. A magnesium atom is present at the metal-ligandbonding site in the Figure. Chlorophyll a exhibits absorption maxima at409 nm, 429 nm, 498 nm, 531 nm, 577 nm, 613 nm, and 660 nm. Chlorophyllb is characterized by R═CHO exhibits absorption maxima at 427 nm, 453nm, 545 nm, 565 nm, 593 nm, and 642 nm. It can be readily seen thatvarious types of chlorophyll, or combinations thereof, can be used astopically applied chromophores to assist the absorption of certainwavelengths of light delivered through the skin or soft tissue forvarious treatments. When used to enhance the absportion of a wavelengthof light that coincides with an absorption maxima of target cells suchas human fibroblasts, treatment can be even more effective or can becarried out with reduced light intensities or can produce multiplebeneficial effects, such as treating acne bacteria and reducing oreliminating acne scarring.

The alkaline hyrolysis of chlorophyll opens the cyclopentanone ring andreplaces the methyl and phytyl ester groups with sodium or potassium.These resulting salts are called chlorophyllins and are water soluble.The alkaline hydrolysis of the chlorophyll shown in FIG. 2 will resultin a NaMg Chlorophyllin, but other salts can easily be formed byreplacing the Mg atom in the chlorophyll with other metals or reactivetransition metals, for example, such as copper, aluminum, iron, metalchelates, or antibody complexes. Such a substitution is made by treatingthe chlorophyll with an acid causing the Mg to be removed and replacedby H₂ which, in turn, is easily replaced by other metals.

Unlike artifically synthesized chromophores, naturally occuringchromophores bear the similar attribute of having the metal ligandbonding site which will dissociate the metal ion upon treatment with anacid. The acid content of human skin is sufficient to trigger thisreaction and, in turn, cause the chlorophyll, having lost the metal ion,to become less soluble in water. The resulting chlorophyll, or othernaturally occuring agent that dissociates a metal ion from a ligand bondunder acidic conditions such as porphyrin for example, makes anexcellent topical composition with superior optical properties foracting as a chromophore to enhance low-intensity light therapies. Inanother embodiment of the invention, therefore, the preferredchromophore is a compound having a metal ligand bond that dissociatesthe metal ion under acidic conditions. In one embodiment of theinvention, topical skin care formulations may be used for altering thepH or acidity of the skin.

In addition to being an effective treatment method for reducing andeliminating the presence of common acne bacteria such as is seen in acnevulgaris and for safely treating conditions such as pseudofolliculitisbarbae, acne rosacea, and sebaceous hyperplasia, the present inventionalso has application to the reduction of cellulite. Using any of thelight sources suitable for use as described herein, adipocyte cells canbe photomodulated. Photomodulation increases the local microcirculationin the cellulite and alters the metabolic activity of the cells.Enhanced local microcirculation, metabolism or enzymation activity, orcombinations thereof, may be produced by photomodulatory means. Toenhance the treatment, any of the topical chromophores as previouslydescribed can be used or non-chromophoric compositions can be used inconjunction with any of the photomodulatory methods, includinglow-intensity light therapy. Further photothermal means may be used todestroy adipocyte cells alone or in combination with photomodulatorymeans, with or without the use of exogenous chromophores.

Many living organisms—both animals and plants—have as one of their majordefense mechanisms against environmental damage to their cells and DNArepair system. This system is present in many if not all livingorganisms ranging from bacteria and yeasts to insects, amphibians,rodents and humans. This DNA mechanism is one which is involved inprocesses to minimize death of cells, mutations, errors in copying DNAor permanent DNA damage. These types of environmental and disease anddrug related DNA damage are involved in aging and cancer.

One of these cancers, skin cancer, results from ultraviolet light damageto the DNA produced by environmental exposure to natural sunlight.Almost all living organisms are unavoidably exposed to sunlight and thusto these damaging UV rays. The damage which is produced is a change inthe structure of the DNA called pyrimidine dimmers. This causes the DNAstructure to be altered so that it cannot be read or copied any longerby the skin cells. This affects genes and tumor development and properfunctioning of the immune system.

An enzyme called photolyase helps to restore the original structure andfunction of the damaged DNA. Interestingly photolyases are activated byligh and act to repair the DNA damaged by ultraviolet light In the darkit binds to the cyclobutane pyrimidine dimmer created by the UV lightand converts it into two adjacent pyrimidines (no dimer connecting theseany longer) and thus the DNA damage is repaired. This direct reversal ofDNA damage is called “photoreactivation”. The photolyase upon exposureto blue light absorbs the light energy and uses this energy to ‘split’the dimer and thus restore the normal DNA structure. Other mechanisms ofDNA repair exist as well.

The photolyase repair mechanism is not well understood at present, butnaturally occurring or synthetic or genetically engineered photolyasefrom essentially any living organism source can be utilized for otherorganisms including human and veterinary and plant applications. DNAdamage produced by factors other than ultraviolet light may also berepaired including, but not limited to, such factors as otherenvironmental damage or toxins, radiation, drugs, diseases, chemotherapyfor cancer, cancer, microgravity and space travel related damage, and amyriad of other causes.

The use of such naturally derived or artificially created or geneticallyengineered photolyase enzymes or related enzymes or other proteinsfunctioning for DNA or RNA repair have a wide variety of applications.For example, the ability to treat skin damaged by sunlight/ultravioletlight of disease and to repair, reverse, diminish or otherwise reducethe risk of skin cancer could be used either as a theraputic treatmentor as a preventive measure for people with severely sundamaged skin,with precancerous skin lesions, or with skin cancer.

This principle applies not only to skin cells and skin cancer but to avery broad range of skin and internal disorders, diseases, dysfunctions,genetic disorders, damage and tumors and cancers. In fact potentiallyany living cells might have beneficial effects from treatment withphotolyase or similar proteins in combination with light therapy.

While in nature the light to activate the photolyase typically comesfrom natural sunlight, essentially any light source, laser and nonlaser, narrow band or broader bandwidth sources can activate thephotolyase if the proper wavelengths and treatment parameters areselected. Thus natural sunlight filtered through a selective sunscreencould be used to activate both native and exogenously appliedphotolyases. Another treatment option would be to apply the photolyaseand then treat with a controlled light source exposure to the properwavelength band and parameters. A wide variety of light sources could beutilized and the range of these is described elsewhere in thisapplication. For example a low energy microwatt narrow band butmultispectral LED light source or array with mixed wavelengths could beutilized. Another embodiment is a filtered metal halide light sourcewith a dominant wavelength of 415 nm +/−20 nm and an exposure of 1-30minutes at 1-100 milliwatts output can be utilized. Such exposure wouldoccur mintues to days after application of a topical product containingphotolyase.

Another example would be the repair of cells in the skin which haveenvironmental damage but instead of repairing the cells which lead toskin cancer the cells which lead to aging (photoaging) of the skin aretargeted for this therapy. In one embodiment, kin fibroblasts which havebeen sun damaged are treated with a photolyase and subsequently thephotolyase is photomodulated with blue light to set in motion the DNArepair mechanism of photolyase—that is photoreactivation. This allowsthe repair of the structure and thus the normal functioning of thefibroblast DNA thus allowing normal functioning and proliferation ofthese fibroblasts—which produce the proteins such as collagen andelastin and hyaluronic acid and matrix ground substance which cause skinto be firm and elastic and youthful in appearance—thus producinganti-aging or skin rejuvenation effects in the skin as well as improvingthe structure and healthy function of the skin.

Various cofactors which are involved in this photoreactivation processcan also be added either topically or systemically to further enhance orimprove the efficiency of this process. Other cofactors needed in theproduction of these proteins once the cells recover normal function alsomay be added topically or systemically to enhance the anti-aging or skinrejuevenation process. The delivery of both the photolyase and/or thecofactors described above can be enhanced by utilizing ultrasound toincrease skin permeability or to increase transport across the skinbarrier and into the skin and underlying tissues. Removal of a portionof the stratum corneum of the skin can also be used, alone orincombination with ultrasound, to enhance penetration and delivery ofthese topically applied agents. Additionally such methods of removing oraltering the stratum corneum can assist in penetration of the light orthe efficiency of same or allow use of lower powered light sourcesincluding home use devices such as battery powered LED sources.

A variety of sources exist for obtaining photolyases. These may includenative naturally occurring photolyases, compounds derived from otherliving organisms (that is one may use for example bacterially derived,or yeast derived, or plankton rederived, or synthetic or geneticallyengineered, etc., photolyases and use them in human skin for beneficialeffects thus not limited to same species derived photolyases. One knownphotolase is derived from Anacystis nidulans while others can be derivedfrom bacteria—yeast in fact protect themselves with a photolyase whichcan be used in humans, other microorganisms, plants, insects, amphibianand animal sources exist.

The photolyase enzymes function by light induced electron transfer froma reduced FAD factor to the environmental exposure produced pyrimidinedimers. The use of free radical inhibitors or quenchers such asantioxidants can also be used to supplement the photolyase therapy.Other light activated chromophores may be utilized with light sourcesand properly selected parameters to further enhance, stimulate,photomodulate, photoactivate or photoinhibit the target or supportingcells or tissue to promote the most effective treatment.

There are many causes of free radical damage to cells. In one embodimentwound healing can be accelerated by utilizing a combination ofantioxidants, cell growth factors, direct photomodulation(photoactivation) of cells, and photoreactivation through photolyases.Topical or systemic therapy with the proper cofactors and replacing anydeficiencies of cofactors can further enhance wound healing. Forexample, a chonic leg ulcer wound could be treated with an antioxidantmixture of vitamin E, vitamin C and glutathione, as well as cofactorssuch as fatty acids and keto acids and low level light therapy using andLED array with parameters selected to photostimulate fibroblasts andepithelial cells could also receive treatment with a photolyase and bluelight therapy thus greatly accelerating wound healing and healing woundsor burns that would otherwise not be treatable.

The potential uses of photolyases and light therapy include: thetreatment or repair or reverse nerve damage or diseases including spinalcord injuries and diseases; cancer or cancer treatment related problemsincluding radiation and chemotherapy; cervical dysplasia and esophagealdysplasia (Barrett's esophagus) and other epithelial derived cell ororgan disorders such as lung, oral cavity, mucous membranes, etc.; eyerelated diseases including but not limited to macular degeneration,cataracts, etc.

There are very broad health and commercial applications of photolyasemediated photorepair or photoreactivation of DNA (or RNA) damage withflavin radical photoreduction/DNA repair via photomodulation or nativeor exogenously applied natural or synthetic or genetically engineeredphotolyases. The addition of topical. Oral, or systemically administeredphotolyases and also their cofactors or cofactors of the cells whose DNAis being repaired further enhance these applications. The enhanceddelivery of such substances topically via ultrasound assisted delivery,via alteration of the skin's stratum corneum, and/or via specialformulations or via special delivery vehicles or encapsulations are yetan additional enhancment to this process.

There are also blue light photoreceptors such as cryptochrome whichphotomodulate the molecular clocks of cells and the biological orcircadian rhythm clocks of animals and plants—that is the mechanismwhich regulates organism response to solar day/night rhythms in livingorganisms. These protein photoceceptors include vitamin B basedcrytochromes. Humans have two presently identified cryptochromegenes—which can be directly or indirectly photomodulated (that isphotoactivated or photoinhibited).

The clinical applications include treatment of circadian rhythmdisorders such as ‘jet lag’, shift work, etc, but also insomnia, sleepdisorders, immune dysfunction disorders, space flight related, prolongedunderwater habitation, and other disturbances of circadian rhythm inanimals. Circadian issues also exist for many other living organismsincluding the plant kingdom.

Warts can be treated using exogenous or endogenous chromophores witheither photothermal or non thermal photomodulation techniques—or acombination of both. Examples of preferred embodiments of endogenouschromophores include the targeting of the vascular blood supply of thewart with either method. Anther preferred embodiment is the use of atopically applied or injected or ultrasonically enhanced delivery ofsuch a chromophore into the wart or its blood supply or supportingtissues with subsequent photomodulation or photothermal activation ofthe chromophore.

One such example would be that of a chlorophyll topical formulationsimilar to those described elsewhere in this application but of higherconcentration and vehicle and particle size optimized for wart therapyand the anaotomic location of the warts (for example warts on thethicker skin of the hand might be formulated differently than that usedfor vaginal warts). An LED light source could be used for home use with644 nm in a battery powered unit wherein the topical formula was applieddaily and treatment of individual warts was performed with the properparameters until the warts disappeared.

For the situation of vaginal warts, a cyclindrical device with an arrayof LED arranged and optically diffused such that the entire vaginalcavity could be properly illuminated in a medically performed procedurewould represent another embodiment of this therapy. A wide range ofsubstances can be utilized either as the primary chromophore or asadjunctive supporting therapy. These compounds are listed elsewhere inthis application. In another embodiment an immune stimulator is utilizedin conjunction with photomodulation with or without an exogenouschromophore. In yet another embodiment a higher powered light sourceeither narrow or broad band can e utilized with the same chromophoretherapy as outlined above, but with parameters selected so that theinteraction with the chromophore is non photomodulation, but ratherintense photothermal effect so as to damage or destroy the wart but withminimal damage to surrounding uninvolved and non supporting tissues.

In one embodiment a chlorophyll and carotenoid topical formulation isapplied and natural sunlight with or without a selective sunscreen areused to interact with the topical formulation. Another embodimentutilizes an injected or ultrasonically enhanced topical delivery of adye such as indocyanine green which has been used for vascularinjections safely in other medical applications.

Papulosquamous, eczematous and psoriasiform and related skin disorderscan be improved, controlled, reduced or even cleared by the samephotomodulation or photothermal interaction with endogenous or exogenouschromophores. The process outlined for warts and the other disorders inthis application may be used for such therapies. The use of ultrasoundis particularly useful in the more scaly disorders in this group ofdiseases as are enzyme peels and other methods with gently removescaling skin. Penetration of light into psoriasis presents for example amajor problem with current therapies. Penetration of drugs and topicalagents is likewise a major theraputic challenge. If the dry skin on topof psoriasis is removed it is well known that this stimulates furthergrowth of the plaque or lesion of psoriasis—yet removal is needed toallow the drugs to penetrate and for light to penetrate. Currentlyalmost all psoriasis light therapy is ultraviolet light and thus therisk of skin cancer and also of photoaging is very significant with alifetime of repeated ultraviolet light therapy. Also such therapytypically involves treating large areas or even the entire body(standing in a large light therapy unit is like being in a tanning bedwhich is standing upright). Thus not only does the skin with psoriasislesions get treated, but also all the normal uninvolved skin typicallygets exposed to the damaging ultraviolet light.

Furthermore typical psoriasis treatments involve the use of oral drugscalled psoralens. These drugs cross link DNA and are light activated.Thus DNA damage in produced not only by the ultraviolet light itself(like being out in sunlight but primarily ultraviolet A light), but inaddition the psoralen drug produced DNA damage. Safety in children in anobvious concern as is use in pregnant or childbearing women.

The use of a topical light activated exogenous chromophore such as mostof the agents listed in this application present no risk of DNA damageand also are generally very safe products—many are natural such aschlorophyll and can be safely used in children and pregnancy and childbearing age women. In addition the treatment is only activated where thetopical agent is applied—unlike the use of oral psoralen drugs thatactivate not only the entire skin but also the retina and other tissues.The light used for this therapy is not only low in power, but it is forthe most part visible or infrared light and is not ultraviolet-producingno DNA damage.

Thus the use of photomodulation or photothermal activation of exogenouslight activated chromophores such as described herein represents asignicant advance in safety and efficacy.

The photolyase embodiments described above also have some applicationfor diseases such as psoriasis. For some cases of psoriasis are veryextensive covering large amounts of the surface area of the body and maybe resistant to other known therapies. The application of a topicalfomulation to the areas not being treated—or to all the body areasexposed to the traditional psoriasis phototherapy could receive a posttreatment with the photolyase and blue light therapy—think of this as atype of ‘antidote’ to the ultraviolet psoriasis phototherapy wherein therepair of DNA damage to normal tissue was facilitated immediatelyfollowing the psoriasis therapy—thus reducing significantly the risk ofskin cancer and photoaging in future years.

Another embodiment involves the use of such a photolyase preparation inthe evening after returning from a long day of occupational sun exposureor after an accidental sunburn. A spray or lotion containing thephotolyase could be applied and then photorepair/photoreactivation ofthe acutely damaged DNA in the skin could be performed—and this could beperformed with a large beam diameter home therapy unit—of by a whitelight source which contained enough of the desired wavelength at theproper parameters to produce this reaction. Additionally an antioxidantskin formulation could be also applied to minimize erythema and otherundesired effects of the sunburn. One such embodiment would be thepreparation described earlier with a combination of vitamin C, vitamin Eand glutathione and free fatty acids and one or more keto acids. Asimilar formulation could contain these agents but utilize only one ortwo of the three antioxidants listed.

In vitro fertilization processes can also be enhanced byphotomodulation—with or without an exogenous chromophore. This cansimply target the cells or subcellular components themselves, asdescribed in the applicants copending U.S. patent application Ser. No.09/894,899 entitled “Method and Apparatus for Photomodulation of LivingCells”, which is hereby incorporated by reference in its entirety.

This can result in a greater success rate of fertilization and/or growthof embryos or other desirable effects on this process. In one embodimentan LED light source is used to treat sperm of animals or humans orgenetically engineered embryos or subcomponents thereof to enhancefertilization.

In another embodiment photolyase or other photoreparative or lightactivated DNA repair proteins or substances combined withphotomodulation can be utilized to ‘correct’ DNA damage in embryonictissues thus generating a normal or more normal embryo. This can beperformed in vitro or in utero (utilizing tiny fiber optic delivery ofthe proper light parameters—or the light can be delivered from outsidethe body into the womb without the risk of introducing a fiber opticdevice.

Another process in which photomodulation can be utilized for significantbenefit is in the stimulation of proliferation, growth, differentiation,etc of stem cells from any living organism. Stem cells growth anddifferentiation into tissues or organs or structures or cell culturesfor infusion, implantation, etc (and their subsequent growth after suchtransfer) can be facilitiated or enhanced or controlled or inhibited.The origin of such stem cells can be from any living tissue or organism.In humans stem cells for these embodiments may come from any source inthe human body, but typically originate from the bone marrow, blood,embryo, placenta, fetus, umbilical cord or cord blood, and can be eithernaturally or artificially created either in vivo, ex vivo or in vitrowith or without genetic alteration or manipulation or engineering. Suchtissue can come from any living source of any origin.

Stem cells can be photoactivated or photoinhibited by photomodulation.There is little or no temperature rise with this process althoughtransient local nondestructive intracellular thermal changes maycontribute via such effects as membrane changes or structuredconformational changes.

The wavelength or bandwidth of wavelengths is one of the criticalfactors in selective photomodulation. Pulsed or continuous exposure,duration and frequency of pulses (and dark ‘off’ period) and energy arealso factors as well as the presence, absence or deficiency of any orall cofactors, enzymes, catalysts, or other building blocks of theprocess being photomodulated.

Photomodulation can control or direct the path or pathways ofdifferentiation of stem cells, their proliferation and growth, theirmotility and ultimately what they produce or secrete and the specificactivation or inhibition of such production.

Photomodulation can up-regulate or down-regulate a gene or group ofgenes, activate or inactivate enzymes, modulate DNA activity, and othercell regulatory functions.

Our analogy for photomodulation of stem cells is that a specific set ofparameters can activate or inhibit differentiation or proliferation orother activities of a stem cell. Much as a burglar alarm keypad has aunique ‘code’ to arm (activate) or disarm (inhibit or inactivate)sending an alarm signal which then sets in motion a series of events soit is with photomodulation of stem cells.

Different parameters with the same wavelength may have very diverse andeven opposite effects. When different parameters of photomodulation areperformed simultaneously different effects may be produced (like playinga simple key versus a chord on a piano). When different parameters areused serially or sequentially the effects are also different—in factdepending on the time interval we may cancel out the priorphotomodulation message (like canceling burglar alarm).

The selection of wavelength photomodulation is critical as is thebandwidth selected as there may be a very narrow bandwidth for someapplications—in essence these are biologically active spectralintervals. Generally the photomodulation will target flavins,cytochromes, iron-sulfur complexes, quinines, heme, enzymes, and othertransition metal ligand bond structures though not limited to these.

These act much like chlorophyll and other pigments in photosynthesis as‘antennae’ for photo acceptor molecules. These photo acceptor sitesreceive photons from electromagnetic sources such as these described inthis application, but also including radio frequency, microwaves,electrical stimulation, magnetic fields, and also may be affected by thestate of polarization of light. Combinations of electromagneticradiation sources may also be used.

The photon energy being received by the photo acceptor molecules fromeven low intensity light therapy (LILT) is sufficient to affect thechemical bonds thus ‘energizing’ the photo acceptor molecules which inturn transfers and may also amplify this energy signal. An ‘electronshuttle’ transports this to ultimately produce ATP (or inhibit) themitochondria thus energizing the cell (for proliferation or secretoryactivities for example). This can be broad or very specific in thecellular response produced. The health of the cells and theirenvironment can greatly affect the response to the photo modulation.Examples include hypoxia, excess or lack or ration of proper cofactorsor growth factors, drug exposure (eg. reduced ubiquinone from certainanticholesterol drugs) or antioxidant status, diseases, etc.

The as yet unknown mechanism, which establishes ‘priorities’ withinliving cells, can be photomodulated. This can include even thedifferentiation of early embryos or stem cell population. Exogenouslight activated chromophores may also be used alone or in combinationwith exogenous chromophores. Genetically altered or engineered stemcells or stem cells which have an inborn genetic error or defect oruncommon but desirable or beneficial trait may require a different‘combination’ of parameters than their analogous ‘normal’ stem cells ormay produce different cellular response if use the same combination ofparameters. Using various methods of photomodulation or other techniquesknown in the art more specific cellular effects may be produced by‘blocking’ some ‘channels’ that are photomodulated.

For example, consider an old fashioned juke box, if one selects theproper buttons one will set in motion a series of events resulting inthe playing of a very specific and unique record or song. If however onewere given a broom to push the buttons one would have to block all butthe desired button to be selective. Likewise pushing an immediatelyadjacent button will not produce the desired outcome.

The magnitude of effects on cells may also be very dependent on thewavelength (when other parameters are the same). One such example is thecontrast between irradiating chemical bonds in DNA with 302 nm lightversus 365 nm light—the 302 nm light produces approximately 5000 timesgreater DNA pyrimidine dimers than the 365 nm only a short distance upthe spectrum. Changing the wavelength can also convert the ratio or typeof these dimers. Thus seemingly subtle changes in photomodulation orphotochemical reaction parameters can produce very large and verysignificant differences in cellular effects—even at the subcellularlevel or with DNA or gene expression.

A final analogy is that photo modulation parameters can be much like a‘morse code” to communicate specific ‘instructions’ to stem cells. Thishas enormous potential in practical terms such as guiding or directingthe type of cells, tissues or organs that stem cells develop ordifferentiate into as well as stimulating, enhancing or acceleratingtheir growth (or keeping them undifferentiated).

Another application of photomodulation is in the treatment of cellulite.Cellulite is a common condition which represents a certain outwardappearance of the skin in certain anatomic areas—most commonly on theupper legs and hips which is widely regarded as cosmeticallyundesirable. Cellulite is the result of a certain anatomic configurationof the skin and underlying soft tissues and fat which may involveabnormalities of circulation or microcirculation or metabolicabnormalities—predominantly in the fat and supporting tissues.Photomodulation or photothermal treatments of the adipocytes (fat cells)or their surrounding supporting structures and blood supply alone or incombination can reduce the appearance of cellulite and/or normalize thestructure and function of the tissues involved with the cellulite.

Photomodulation of adipocytes can be performed using endogenouschromophores suche as the adipocytes themselves, their mitochondria orother targets within the adipocyte electron transport system orrespiratory chain or other subcellular components. Exogenous light orelectromagnetically activated chromophores can also be photomodulated(photoactivated or photoinhibited) or photothermal interactions can alsooccur. Examples of such chromophores are listed elsewhere in thisapplication and can be topically or systemically introduced into thetarget tissues or adipocytes or surrounding blood vessels. The use ofexternally or internally applied ultrasound can be utilized either toenhance delivery of the chromophore or to alter local circulation or toprovide thermal effect or to provide destructive effect or anycombination of these actions.

In one embodiment the chromophore is delivered into the fat layer underthe skin on the thigh using external ultrasound to enhance skinpermeability and also enhance transport. The alteration of the stratumcorneum alone or in combination with the ultrasound can further enhancedelivery of the chromophore. External massage therapy from varioustechniques can be used to enhance the treatment process. In anotherembodiment chromophore is injected into the fat layer prior o treatmentwith light. Some light therapy with or without ultrasound may be used tophotomodulate or photothermally or ultrasonically increase or otherwisealter the circulation or microciruclation or local metabolic processesin the areas affected by cellulite or other tissues. The proper lightparameters are selected for the target adipocytes, blood vessels ,exogenous chromophores, etc. Since some of the target tissues incellulite are deeper than for example wrinkles or acne, typically longenough wavelengths of light must be utilized so that the lightpenetrated deeply enough to reach the target tissue.

Various topical or systemic agents can also be used to enhance thecellulite reduction treatments. Some of these include various cofactorsfor the metabolic or adipocyte interactions described and have beenpreviously described herein.

Additional topical agents for inhibiting hair growth include inhibitorsof ornithine decarboxylase, inhibitors of vascular endothelial growthfactor (VEGF), inhibitors of phospholipase A2, inhibitors ofS-adenosylmethionine. Specific examples of these, but not limited to,include licorice, licochalone A, genestein, soy isoflavones,phtyoestrogens, vitamin D and derivatives, analogs, conjugates, naturalor synthetic versions or genetically engineered or altered orimmunologic conjugates with these agents.

Also the same topical agents, exogenous light activated chromophores andtreatments described fro cellulite above also are hereby incorporatedinto methods for reducing the growth of hair. Increasing the circulationor microcirculation of the hair bearing skin may also be accomplished bysimply producing vasodilation by any method know to those skilled inthis art. Some examples of topical agents which might be used to createsuch vasodilation include, but are not limited to: capsicum, ginseng,niacinamide, minoxidil, etc.

The present invention is further illustrated by way of the followingexamples.

EXAMPLE 1 Acne Reduction—Continuous Treatment

A team of blinded expert graders viewing before and after photos ofpatients subjected to the non-ablative LILT (“Low Intensity LightTherapy”) of the present invention score the global improvement ofvisible acne prominent in the facial area.

Six females are treated to reduce acne by, first, treating their skinwith a topical composition containing about 2.5%, by weight copperchlorophyllin as the active ingredient. The treatment includessubjecting the target area of the patient's skin that has been treatedwith the topical composition to a filtered fluorescent light operatedcontinously and providing full-face coverage, i.e., the entire face ofthe patient is subjected to the light from the light source. Threetreatments over 12 weeks to the entire face with at a light intensity of11 milliwatts for 15 minutes per treatment session, resulting in a totalenergy exposure of 10.0 J/cm². Thermal injury is produced with bloodvessels included among the target chromophores (but no skin wound careis needed). The average reduction in acne is shown in Table 2. The lightsource has a dominant emissive wavelength in the range of 410 nm to 420nm and is centered at 415 nm. TABLE 2 Averaged Value of Week/ValueReduction 0 weeks 0% 4 weeks 28% 8 weeks 56% 12 weeks  64%

EXAMPLE 2 Acne Reduction—Pulsed Treatment

A team of blinded expert graders viewing before and after photos ofpatients subjected to the non-ablative LILT (“Low Intensity LightTherapy”) of the present invention score the global improvement ofvisible acne on the facial area.

Six females are treated for acne by, first, contacting their skin oncenightly for each night during the 2 weeks preceding the treatementsession with a topical composition containing a mixture of 2.0%chlorophyll a, 2.0% chlorophyll b, and 5% carotenoids as the activeingredients. The laser diode treatment includes subjecting the targetarea of the patient's skin that has been treated with the topicalcomposition to a laser diode light having a pulse width of 800 msec anda pulse frequency of 1 hz (1 pulse per second). Three pulses areadministered. Six treatments over 12 weeks to the entire face with 400nm laser diode with a 10 cm beam diameter at an intensity ranging 2500milliwatts/cm2. The average reduction in acne is shown in Table 3. TABLE3 Averaged Value of Week/Value Reduction 0 weeks 0% 2 weeks 36% 7 weeks58% 12 weeks  82%

EXAMPLE 3 Acne and Acne Scarring Reduction Combined ContinuousWave/Pulsed Treatment

Three females showing active acne and acne scarring in the facial areaare tested for improvement in scar prominence, skin texture, and scarvisibility before and after receiving treatment in accordance with thenon-ablative method of the present invention used in conjunction with atopical composition containing the active ingredient chlorophyll in acarrier suspension of microsponges having a diameter of 5 microns orless. Measurements are taken from by utilizing subjective evaluationsconducted by trained medical personnel. The topical treatment includesapplying the carotenoid composition containing about 5% carotenoids in aliposome carrier (alternatively, microsponges can be used having anaverage diameter of 5 microns) to the skin of the facial area andallowing it to penetrate the stratum corneum for approximately 15-20minutes prior to beginning treatment. The first step in the treatmentprocess is to expose the facial area to a continous wave from a filteredmetal halide lamp having a dominant emissive wavelength, i.e., anemission peak, at about 415 nm +/−5nm and an energy output of 100 mW/cm²for approximately 10 minutes. The patient's facial area is then exposedto a pulsed LED treatment includes subjecting the target chromophorefibroblasts and subcellular components thereof to LED light having apulse width of 250 msec and a pulse spacing of 250 msec for 90 pulses.Six treatments over 12 weeks to the entire face with the metal halidesource as previously described and a 590 nm multichromatic LED, i.e., anLED having an emission peak at about 590 nm and putting out medicallyuseful light in the range of about 585 nm to about 595 nm, at anintensity ranging from 1.05-2.05 μWatts. Further, the treatmentmaintains a skin temperature below the threshold of thermal injury. Theaverage improvement in acne scar visibility is shown in Table 4. Inaccordance with the present invention, this dual-source treatment methodemploys the metal-halide light source to treat the active acne and theLED source to reduce or eliminate the visibility of acne scars. TABLE 4Percent Improvement Pre treatments Post treatments (%) Skin Elasticity 085 Scarring 0 46 Active Acne Lesions 0 79

EXAMPLE 4 Acne Scar Reduction—Pulsed Treatment

A team of blinded expert graders viewing before and after photos ofpatients subjected to the non-ablative LILT (“Low Intensity LightTherapy”) of the present invention score the global improvement ofvisible acne scarring.

Six females were tested for reduction of acne scar visibility. The LEDtreatment includes subjecting the patient's skin to a LED light having apulse width of 250 msec and a pulse spacing of 250 msec for a period of90 pulses. Eight treatments over 16 weeks to the entire face with 590 nmmultichromatic LED at an intensity ranging from 1.0-2.0 μWatts. Having abandwidth of +/−5-15 nm, the LED therefore produces light in thewavelength range of from 575 nm to 605 nm. Also used in a second LEDsource having a dominant emissive wavelength of 870 nm with a bandwidthof +/−30-50 nm. Further, the treatment maintains a skin temperaturebelow the threshold of thermal injury. The average reduction in visibleacne scarring is shown in Table 5. TABLE 5 Week/Value Averaged Value ofReduction 0 weeks 0% 4 weeks 42% 8 weeks 51% 12 weeks  48%

EXAMPLE 5 Acne Reduction—Continuous Light

A method for treating acne by a combination of photothermal andphotomodulatory treatment is used to reduce the presence of acnebacteria, resulting in a substantial reduction in the existence of acneon the facial area. In this example, dual chromophores are targeted. Anative, naturally occurring porphyrin in acne and an exogenouschromophor.

Pretreatment is performed using a topically applied chromophore. In thisexample, the topical chromophore is an aqueous solution of Na CuChlorophyllin and carotenoids is applied to the skin. The skin is firstcleansed with a low residue cleansing solution and then a pH adjustingastringent lotion is applied by a 5-10 minute application of an enzymemask for removing skin debris and a portion of the stratum corneum. Thetopical chromophore is applied and delivery of the chromophore isenhanced with a 3 megahertz ultrasound emitter using a duty cycle of 25%and 1.5 watts output using a massage-like motion to cover the entireface for 5 minutes and the shoulders for 5 minutes. Any excess lotion isthen removed. The cleansing solution used for this example shouldinclude at least 40% of either an acetone, ethyl acetate, orethyl/isopropyl alcohol solvent, from about 1% to about 4% salicylicacid as a penetrant enhancer, and about 5% glycerin, included as amoisturizer.

A filtered fluorescent light source having a dominant emission at 420 nmis set to emit continuously for 20 minutes at an intensity of 10Joules/cm². The entire face and upper back of the patient is treatedwith minimal overlap during each of 6 treatment sessions, each spacedtwo week apart. Approximately an 85% reduction in acne is observed.

EXAMPLE 6 Home-Use Device and Treatment

The treatment method of Example 5 is carried out. The patient continuesthe treatment at home using a home-use device comprising a hand-held LEDdevice, a lotion containing an aqueous solution of about 2%, by weight,chlorophyll and about 2%, by weight, of a carotenoid, and a wavelengthselective sunscreen.

The patient applies a chlorophyll-containing topical solution to theareas previously treated for acne scarring once per day, preferably butnot necessarily in the morning. Further, the patient applies a sunscreentypical of those known in the art except that it is formulated to permitthe passage of radiation having a wavelength in the range of about 400nm to about 420 nm and 600 nm to about 660 nm to allow natural sunlightto further aid the treatment process. The carotenoids provide protectionto the skin against damage from ultraviolet radiation received fromsunlight. Finally, the patient uses the hand-held LED device 1-2 timesper day. The LED device emits radiation having a dominant emission atabout 644 nm +/−5 nm at an energy output of approximately 20 microwattsin a continuous wave. Each treatment session covers active acne lesionsfor acne lesions for approximately 2 minutes. A further reduction in thevisibility of acne scarring is observed. Additional improvement in acnescar reduction can be achieved using a 590 nm multichromatic LED at anintensity ranging from 1.0-2.0 μWatts as described in prior examples.

EXAMPLE 7 Mixed Led Panel Treatment Array

An LED array includes both blue LEDs having a dominant emission at 415nm to treat active acne and yellow LEDs having a dominant emission at590 nm to treat acne scarring. The skin is pretreated in the same manneras described in Example 5. The LED array is then positioned to cover theentire facial area of the patient with a 20 minute continuous wave ofblue light (415 nm) and an exposure of yellow (590 nm) light pulsed onfor 250 millseconds and off for 250 milliseconds. Approximately 100pulses are delivered.

EXAMPLE 8 Sebaceous Gland Size Reduction

Female skin exhibiting active acne rosacea and numeroussebaceoushyperplasia lesions is treated with a metal halide light sourcehaving a dominant emission centered at 475 nm +/−5 nm and an energyoutput of 4.0 mW/cm², pulsed with a code of 250/100/100, approximately10 minutes after having been treated with a topically appliedcomposition containing chlorophyll and carotenoids as the activeingredients. A mixture of 2.0% chlorophyll a and b is used. Allpercentages are by weight. Three treatments are administered at two-weekintervals. Visual inspection shows a reduction in sebaceous gland sizeof 30%-50%.

EXAMPLE 9 Pulsed Treatment for Acne Bacteria

An LED array includes both blue LEDs having a dominant emission at 475nm to treat active acne and secondary LEDs having dominant emissions at590 nm and 870 nm to treat acne scarring. The skin is pretreated in thesame manner as described in Example 5. The LED array is then positionedto cover the entire facial area of the patient with pulsed blue light(475 nm) and an exposure of yellow/IR (590 nm/870 nm) light pulsed onfor 250 millseconds and off for 250 milliseconds. Approximately 100pulses are delivered for both blue and the yellow/IR light.

EXAMPLE 10 Multiple Wavelength Method

The treatment method of Example 5 is carried out. The patient continuesthe treatment at home using a home-use device comprising a hand-held LEDdevice, a lotion containing an aqueous solution of about 2%, by weight,chlorophyll and a wavelength selective sunscreen.

The patient applies a chlorophyll-containing topical solution to theareas previously treated for acne scarring once per day, preferably butnot necessarily in the morning. Further, the patient applies a sunscreentypical of those known in the art except that it is formulated to permitthe passage of radiation having a wavelength in the range of about 400nm to about 700 nm to allow natural sunlight to further aid thetreatment process.

The carotenoids provide protection to the skin against damage fromultraviolet radiation received from sunlight. Finally, the patient usesthe hand-held LED device 1-2 times per day. The LED device emitsradiation from two sources, one have dominant emissions at about 590 nm+/−5 nm at an energy output of approximately 20 microwatts in a pulsedmode, and another having approximately the same parameters at 870 nm.Each treatment session covers active acne lesions for approximately 35seconds with a pulse code of250/100/100. A further reduction in thevisibility of acne scarring is observed.

EXAMPLE 11 Mixed Led Panel Treatment Array

An LED array includes both LEDs having a dominant emission at 425 nm andLEDs having a dominant emission at 660 nm. The skin is untreated with atopical composition. Both LEDs are pulsed simultaneously for 250milliseconds, 100 times. There is an interpulse delay (time betweenpulses) of 100 milliseconds. A light intensity of about 4 mW is used.

EXAMPLE 12 Mixed Led Panel Treatment Array

An LED array includes LEDs having a dominant emission at 660 nm, LEDshaving a dominant emission at 590 nm, and another at 870 nm. The skin isuntreated with a topical composition. All LEDs are pulsed simultaneouslyfor 250 milliseconds, 100 times. There is an interpulse delay (timebetween pulses) of 100 milliseconds, at a light intensity of about 4 mW.

EXAMPLE 13 Single Wavelength Treatment

An LED panel includes LEDs having a dominant emission at 660 nm. Theskin is untreated with a topical composition. The LEDs are pulsedsimultaneously for 250 milliseconds, 100 times. There is an interpulsedelay (time between pulses) of 100 milliseconds, using an LED powerlevel of about 4 mW.

The presently disclosed embodiments are to be considered in all respectsas illustrative and not restrictive, the scope of the invention beingindicated by the appended claims, rather than the foregoing description,and all changes which come within the meaning and range of equivalencyof the claims are therefore intended to be embraced therein.

1. A method, comprising: exposing tissue containing acne bacteria to atleast one source of light having emissions at a wavelength from about300 nm and about 1400 nm; operating the at least one source of light ata power output of about 20 mW or lower; and observing a reduction inacne bacteria present on or in the tissue.
 2. The method of claim 1wherein the acne bacteria is present in or on the tissue selected fromthe group consisting of sebaceous oil glands, sebaceous ducts,sebocytes, supporting tissue thereof, and combinations thereof.
 3. Themethod of claim 1 wherein the source of light is a narrowband,multichromatic electromagnetic radiation.
 4. The method of claim 3wherein the narrowband, multichromatic electromagnetic radiation has adominant emissive wavelength of from about 390 nm to about 1400 nm. 5.The method of claim 4 wherein the dominant emissive wavelength isselected from the group consisting of 400 nm, 420 nm, 430 nm, 445 nm,475 nm, 590 nm, 635 nm, 655 nm, 660 nm, 670 nm, 780 nm, 785 nm, 810 nm,830 nm, 840 nm, 860 nm, 904 nm, 915 nm, 980 nm, 1015 nm, 1060 nm, 1260nm, and 1400 nm.
 6. The method of claim 1 comprising applying aphotomodulation enhancing agent to the tissue containing or surroundingthe acne bacteria.
 7. The method of claim 6 wherein said photomodulationenhancing agent comprises a composition have an active agent selectedfrom the group consisting of at least one of Vitamin C, Vitamin E,Vitamin A, Vitamin K, Vitamin F, Retin A (Tretinoin), Adapalene,Retinol, Hydroquinone, Kojic acid, a growth factor, echinacea, anantibiotic, an antifungal, an antiviral, a bleaching agent, an alphahydroxy acid, a beta hydroxy acid, salicylic acid, antioxidant triadcompound, a seaweed derivative, a salt water derivative, an antioxidant,a phytoanthocyanin, epigallocatechin-3-ganate, a phytonutrient, abotanical product, a herbaceous product, a hormone, an enzyme, amineral, a genetically engineered substance, a cofactor, a catalyst, anantiaging substance, insulin, trace elements (including ionic calcium,magnesium, etc), minerals, Rogaine, a hair growth stimulating substance,a hair growth inhibiting substance, a dye, a natural or syntheticmelanin, a metalloproteinase inhibitor, proline, hydroxyproline, ananesthetic substance, chlorophyll, copper chlorophyllin, chloroplasts,carotenoids, bacteriochlorophyll, phycobilins, carotene, xanthophyll,anthocyanin, and derivatives, subcomponents, and analogs of the above,both natural and synthetic, and mixtures thereof.
 8. The method of claim7 wherein the photomodulation enhancing agent is selected from the groupconsisting of chlorophyll, carotenoids, bacteriochlorophyll,phycobilins, porphyrins, derivatives thereof, and mixtures thereof. 9.The method of claim 1 further comprising subjecting the photomodulationenhancing agent to a penetration enhancing procedure prior to exposingsaid photomodulation enhancing agent to said source of electromagneticradiation.
 10. The method of claim 9 wherein the penetration enhancingprocedure comprises a procedure selected from the group consisting ofenzyme peel, microderm abrasion, solvent stripping, tape stripping,scrubbing, laser ablation, laser vaporization, chemical peeling,electrical stimulation, laser treatments using high peak power and shortpulse durations, ultrasound, or combinations thereof.
 11. The method ofclaim 9 wherein the penetration enhancing procedure comprisesmicrodermabrasion.
 12. The method of claim 9 wherein the penetrationenhancing procedure comprises exposing said photomodulation enhancingagent to ultrasound.
 13. The method of claim 4 wherein the source ofnarrowband, multichromatic electromagnetic radiation is a light emittingdiode.
 14. The method of claim 13 wherein the energy output of the lightemitting diode is from about 0.5 mW to about 20 mW.
 15. The method ofclaim 14 wherein the energy output of the light emitting diode is about4 mW.
 16. The method of claim 15 wherein the light emitting diode has adominant wavelength selected from 400 nm, 420 nm, 430 nm, 445 nm, 475nm, 590 nm, 635 nm, 655 nm, 660 nm, 670 nm, 780 nm, 785 nm, 810 nm, 830nm, 840 nm, 860 nm, 904 nm, 915 nm, 980 nm, 1015 nm, 1060 nm, 1260 nm,and 1400 nm.
 17. A method, comprising: exposing acne bacteria to atleast one source of narrowband, multichromatic electromagnetic radiationhaving at least one dominant emissive wavelength between about 300 nmand about 1400 nm and a power output of from about 0.5 mW to about 20 mWcontinuously for a time of from about 0.5 minutes to about 60 minutes.18. The method of claim 17 wherein the tissue is continuously exposed tothe source of narrowband, multichromatic electromagnetic radiation for atime of about 15 minutes.
 19. The method of claim 17 wherein the theenergy output of the source of narrowband, multichromaticelectromagnetic radiation is about 4 mW.
 20. The method of claim 17comprising applying a photomodulation enhancing agent to the tissuecontaining or surrounding the acne bacteria.
 21. The method of claim 20wherein said photomodulation enhancing agent comprises a compositionhave an active agent selected from the group consisting of at least oneof Vitamin C, Vitamin E, Vitamin A, Vitamin K, Vitamin F, Retin A(Tretinoin), Adapalene, Retinol, Hydroquinone, Kojic acid, a growthfactor, echinacea, an antibiotic, an antifungal, an antiviral, ableaching agent, an alpha hydroxy acid, a beta hydroxy acid, salicylicacid, antioxidant triad compound, a seaweed derivative, a salt waterderivative, an antioxidant, a phytoanthocyanin,epigallocatechin-3-ganate, a phytonutrient, a botanical product, aherbaceous product, a hormone, an enzyme, a mineral, a geneticallyengineered substance, a cofactor, a catalyst, an antiaging substance,insulin, trace elements (including ionic calcium, magnesium, etc),minerals, Rogaine, a hair growth stimulating substance, a hair growthinhibiting substance, a dye, a natural or synthetic melanin, ametalloproteinase inhibitor, proline, hydroxyproline, an anestheticsubstance, chlorophyll, copper chlorophyllin, chloroplasts, carotenoids,bacteriochlorophyll, phycobilins, carotene, xanthophyll, anthocyanin,and derivatives, subcomponents, and analogs of the above, both naturaland synthetic, and mixtures thereof.
 22. The method of claim 20 whereinthe photomodulation enhancing agent is selected from the groupconsisting of chlorophyll, carotenoids, bacteriochlorophyll,phylocibins, porphyrins, derivatives thereof, and mixtures thereof. 23.The method of claim 20 further comprising subjecting the photomodulationenhancing agent to a penetration enhancing procedure prior to exposingsaid photomodulation enhancing agent to said source of electromagneticradiation.
 24. The method of claim 23 wherein the penetration enhancingprocedure comprises a procedure selected from the group consisting ofenzyme peel, microderm abrasion, solvent stripping, tape stripping,scrubbing, laser ablation, laser vaporization, chemical peeling,electrical stimulation, laser treatments using high peak power and shortpulse durations, ultrasound, or combinations thereof.
 25. The method ofclaim 24 wherein the penetration enhancing procedure comprisesmicrodermabrasion.
 26. The method of claim 24 wherein the penetrationenhancing procedure comprises exposing said photomodulation enhancingagent to ultrasound.
 27. A method, comprising: exposing acne bacteria toat least one source of narrowband, multichromatic electromagneticradiation having at least one dominant emissive wavelength between about300 nm and about 1400 nm and a power output of from about 0.5 mW toabout 20 mW, wherein the source of narrowband, multichromaticelectromagnetic radiation is pulsed at least 2 times.
 28. The method ofclaim 27 wherein the tissue is exposed to about 2 to about 2000 pulsesfrom the source of narrowband, multichromatic electromagnetic radiation.29. The method of claim 28 wherein each pulse is from about 1millisecond to about 1000 milliseconds.
 30. The method of claim 29wherein each pulse is separated by from about 1 to about 1000milliseconds.
 31. The method of claim 27 wherein the source ofnarrowband, multichromatic electromagnetic radiation is pulsed about 100times for about 250 milliseconds per pulse with a separation of about100 milliseconds between each pulse.
 32. The method of claim 31 whereinthe the energy output of the source of narrowband, multichromaticelectromagnetic radiation is about 4 mW.
 33. The method of claim 27comprising applying a photomodulation enhancing agent to the tissuecontaining or surrounding the acne bacteria.
 34. The method of claim 33wherein said photomodulation enhancing agent comprises a compositionhave an active agent selected from the group consisting of at least oneof Vitamin C, Vitamin E, Vitamin A, Vitamin K, Vitamin F, Retin A(Tretinoin), Adapalene, Retinol, Hydroquinone, Kojic acid, a growthfactor, echinacea, an antibiotic, an antifungal, an antiviral, ableaching agent, an alpha hydroxy acid, a beta hydroxy acid, salicylicacid, antioxidant triad compound, a seaweed derivative, a salt waterderivative, an antioxidant, a phytoanthocyanin,epigallocatechin-3-ganate, a phytonutrient, a botanical product, aherbaceous product, a hormone, an enzyme, a mineral, a geneticallyengineered substance, a cofactor, a catalyst, an antiaging substance,insulin, trace elements (including ionic calcium, magnesium, etc),minerals, Rogaine, a hair growth stimulating substance, a hair growthinhibiting substance, a dye, a natural or synthetic melanin, ametalloproteinase inhibitor, proline, hydroxyproline, an anestheticsubstance, chlorophyll, copper chlorophyllin, chloroplasts, carotenoids,bacteriochlorophyll, phycobilins, carotene, xanthophyll, anthocyanin,and derivatives, subcomponents, and analogs of the above, both naturaland synthetic, and mixtures thereof.
 35. The method of claim 33 whereinthe photomodulation enhancing agent is selected from the groupconsisting of chlorophyll, carotenoids, bacteriochlorophyll,phycobilins, porphyrins, derivatives thereof, and mixtures thereof. 36.The method of claim 33 further comprising subjecting the photomodulationenhancing agent to a penetration enhancing procedure prior to exposingsaid photomodulation enhancing agent to said source of electromagneticradiation.
 37. The method of claim 36 wherein the penetration enhancingprocedure comprises a procedure selected from the group consisting ofenzyme peel, microderm abrasion, solvent stripping, tape stripping,scrubbing, laser ablation, laser vaporization, chemical peeling,electrical stimulation, laser treatments using high peak power and shortpulse durations, ultrasound, or combinations thereof.
 38. The method ofclaim 37 wherein the penetration enhancing procedure comprisesmicrodermabrasion.
 39. The method of claim 37 wherein the penetrationenhancing procedure comprises exposing said photomodulation enhancingagent to ultrasound.